Structural insight into the UNC-45–myosin complex
Article first published online: 10 APR 2013
Copyright © 2013 Wiley Periodicals, Inc.
Proteins: Structure, Function, and Bioinformatics
Volume 81, Issue 7, pages 1212–1221, July 2013
How to Cite
Fratev, F., Ósk Jónsdóttir, S. and Pajeva, I. (2013), Structural insight into the UNC-45–myosin complex. Proteins, 81: 1212–1221. doi: 10.1002/prot.24270
- Issue published online: 17 JUN 2013
- Article first published online: 10 APR 2013
- Accepted manuscript online: 14 FEB 2013 07:01AM EST
- Manuscript Accepted: 31 JAN 2013
- Manuscript Revised: 6 JAN 2013
- Manuscript Received: 4 OCT 2012
- molecular dynamics;
The UNC-45 chaperone protein interacts with and affects the folding, stability, and the ATPase activity of myosins. It plays a critical role in the cardiomyopathy development and in the breast cancer tumor growth. Here we propose the first structural model of the UNC-45–myosin complex using various in silico methods. Initially, the human UNC-45B binding epitope was identified and the protein was docked to the cardiac myosin (MYH7) motor domain. The final UNC45B–MYH7 structure was obtained by performing of total 630 ns molecular dynamics simulations. The results indicate a complex formation, which is mainly stabilized by electrostatic interactions. Remarkably, the contact surface area is similar to that of the myosin-actin complex. A significant interspecies difference in the myosin binding epitope is observed. Our results reveal the structural basis of MYH7 exons 15–16 hypertrophic cardiomyopathy mutations and provide directions for drug targeting. Proteins 2013; 81:1212–1221. © 2013 Wiley Periodicals, Inc.